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Has anyone working at a SA clinic not been able to treat heartworm positive patients because of a total lack of immiticide (melarsomine)? The clinic where I currently work has five heartworm positive dogs and we can't get enough immiticide to treat them all. I work at a clinic that caters to a very wealthy area so we rarely have heartworm tests come back positive so the timing of it all just seems horrible. It also doesn't help that except for one, all of the dogs are large so they require even more of the drug.
 

cowgirla

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Has anyone working at a SA clinic not been able to treat heartworm positive patients because of a total lack of immiticide (melarsomine)? The clinic where I currently work has five heartworm positive dogs and we can't get enough immiticide to treat them all. I work at a clinic that caters to a very wealthy area so we rarely have heartworm tests come back positive so the timing of it all just seems horrible. It also doesn't help that except for one, all of the dogs are large so they require even more of the drug.

We were told that the shortage simply means we can't order it until we KNOW we need it, and we can only order as much as we will use immediately...
Basically, that there is a lack, and they are compensating for that by not allowing clinics to keep it on their shelves in the pharmacy, "just in case" and instead, the company itself is holding on to what they have and dispensing as necessary.

We had two come up positive in the past few weeks. Called our supplier, told them what dosage we needed, and the immiticide was at our doorstep the next morning, without a problem. Ours were both big retrievers, too.

So I'm really not sure?
 

laurauva2009

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Yep we havent been able to get any in the last couple of months. I know there was an article on DVM360 about the shortage. I believe they are trying to ration what is left so the vet is supposed to fill out a form explaining how sick the dog is on a scale of 1-5 and only the worst cases will get any, except I am pretty sure we have filled that out and still havent gotten any.

I just found this on a JAVMA article

"Dr. Zack Mills, vice president of sales for Merial, wrote in a Dec. 1, 2009, letter to veterinarians that unforeseen technical difficulties during a planned manufacturing site transfer led to limitations in the supply of Immiticide for the first quarter of 2010."
 

DVMDream

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Has anyone working at a SA clinic not been able to treat heartworm positive patients because of a total lack of immiticide (melarsomine)? The clinic where I currently work has five heartworm positive dogs and we can't get enough immiticide to treat them all. I work at a clinic that caters to a very wealthy area so we rarely have heartworm tests come back positive so the timing of it all just seems horrible. It also doesn't help that except for one, all of the dogs are large so they require even more of the drug.

WOW! Five heartworm positive dogs. I think I have only seen 2 heartworm positive dogs in five years. Heartworms must be much more common where you are at because it is rare for us to see heartworm positive dogs. I did not know about the lack of immiticide that is terrible that it has happened at the worst possible time. Hopefully, the company will be able to get you some of it soon.
 

Whyevernot55

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WOW! Five heartworm positive dogs. I think I have only seen 2 heartworm positive dogs in five years. Heartworms must be much more common where you are at because it is rare for us to see heartworm positive dogs. I did not know about the lack of immiticide that is terrible that it has happened at the worst possible time. Hopefully, the company will be able to get you some of it soon.
Looks like the OP is in Texas, which has TONS of heartworm. I'm in Cleveland - we NEVER used to see heartworm, but it's become a lot more prevalent in the last 5 years. After Hurricane Katrina, a lot of those animals came up here - and all over the country, really. And 99% of those dogs were heartworm positive, so everywhere they went, the local mosquito population picked it up and now it's more prevalent in areas that it never used to exist. We saw at least 5 cases in 2009, whereas in the past we saw maybe 1 or 2 a year.
 

DVMDream

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Looks like the OP is in Texas, which has TONS of heartworm. I'm in Cleveland - we NEVER used to see heartworm, but it's become a lot more prevalent in the last 5 years. After Hurricane Katrina, a lot of those animals came up here - and all over the country, really. And 99% of those dogs were heartworm positive, so everywhere they went, the local mosquito population picked it up and now it's more prevalent in areas that it never used to exist. We saw at least 5 cases in 2009, whereas in the past we saw maybe 1 or 2 a year.
I guess they decided to stay away from AZ because we are still a heartworm deadzone, for the most part. Maybe the extreme "dry heat" has something to do with it...120 anyone?
 

Ben and Me

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I guess they decided to stay away from AZ because we are still a heartworm deadzone, for the most part. Maybe the extreme "dry heat" has something to do with it...120 anyone?
Mosquitos breed (or have some vital stage of their life cycle) in puddles and other stagnant water, so if you are in the middle of the dry desert, you probably don't have much of that around! :)

I wonder if they have HW up in Alaska? I've heard the mosquitos up there are killer.

It's very common in the south - most rescue dogs that haven't been on prevention are HW positive. I've heard that, "In the South, it's not 'if' your dog will get heartworms - it's when"

I've heard people talk (on the internet, so take it with a grain of salt) about a "slow kill method" using Heartgard - I wonder if that would be an option for these pups?
 

cowgirla

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Looks like the OP is in Texas, which has TONS of heartworm. I'm in Cleveland - we NEVER used to see heartworm, but it's become a lot more prevalent in the last 5 years. After Hurricane Katrina, a lot of those animals came up here - and all over the country, really. And 99% of those dogs were heartworm positive, so everywhere they went, the local mosquito population picked it up and now it's more prevalent in areas that it never used to exist. We saw at least 5 cases in 2009, whereas in the past we saw maybe 1 or 2 a year.

Past couple years, HW has really made its way into New England. A lot of it is the rescue dogs coming from down south, unfortunately, but our weather has been pretty conducive to skeeter-life, which doesn't help either.

And of course, half our clients think "Oh, HW is only a problem down south, so I don't waste my money on prevention...." UGH! Even if we practically give the preventative away for free, some people still won't use it.

Two cases already for 2010, and we saw 3 cases in 2009, and 5 in 2008.
 

cowgirla

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Mosquitos breed (or have some vital stage of their life cycle) in puddles and other stagnant water, so if you are in the middle of the dry desert, you probably don't have much of that around! :)

I wonder if they have HW up in Alaska? I've heard the mosquitos up there are killer.

It's very common in the south - most rescue dogs that haven't been on prevention are HW positive. I've heard that, "In the South, it's not 'if' your dog will get heartworms - it's when"

I've heard people talk (on the internet, so take it with a grain of salt) about a "slow kill method" using Heartgard - I wonder if that would be an option for these pups?

I thought Heartgard didn't have the capabilities of killing the adult worms, it only killed the larvae, at the weight dosages on the box?
 

Whyevernot55

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I've heard people talk (on the internet, so take it with a grain of salt) about a "slow kill method" using Heartgard - I wonder if that would be an option for these pups?
Yup, it's true - this is actually the method we use most because it is MUCH cheaper and has fewer side effects than using Immiticide. Heartgard Plus is pretty safe, and generally well tolerated. You can't do it in dogs with really heavy worm loads, but most of the time when the dogs aren't having symptoms yet, the load is small. It can take 18-24 months for the dog to test negative, but it's effective. The dogs get tested every 6 months until they test negative.
We just had a clinic meeting about HW because the season is about to get into swing here. It's interesting stuff - I love studying parasites.
 

Whyevernot55

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I thought Heartgard didn't have the capabilities of killing the adult worms, it only killed the larvae, at the weight dosages on the box?
My understanding is that it slowly weakens the adult worms until they die. Like I said above, it's not effective for dogs with high parasitemia, but for small worm loads it works.
 

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Yup, it's true - this is actually the method we use most because it is MUCH cheaper and has fewer side effects than using Immiticide. Heartgard Plus is pretty safe, and generally well tolerated. You can't do it in dogs with really heavy worm loads, but most of the time when the dogs aren't having symptoms yet, the load is small. It can take 18-24 months for the dog to test negative, but it's effective. The dogs get tested every 6 months until they test negative.
We just had a clinic meeting about HW because the season is about to get into swing here. It's interesting stuff - I love studying parasites.
It was my understanding that this is not true- we were told that prophylactics like heartgard only work on L3 and L4's less than 45 days old, so you're not preventing infection, only development of disease. If the animal tests heartworm positive it's indicating the presence of adult females that will not be affected by heartgard and that can continually produce microfilaria, which will perpetuate the problem if mosquitoes feed on that animal, as well as cause disease themselves.

As always I could be wrong, but I hope not since our test is tomorrow :p
 

DVMDream

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Mosquitos breed (or have some vital stage of their life cycle) in puddles and other stagnant water, so if you are in the middle of the dry desert, you probably don't have much of that around! :)
You would think not, but with all of the backyard pools here and people who do not know how to clean their pools. We have nice little breeding grounds for mosquitos right in people's backyards. :mad:
 

Whyevernot55

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It was my understanding that this is not true- we were told that prophylactics like heartgard only work on L3 and L4's less than 45 days old, so you're not preventing infection, only development of disease. If the animal tests heartworm positive it's indicating the presence of adult females that will not be affected by heartgard and that can continually produce microfilaria, which will perpetuate the problem if mosquitoes feed on that animal, as well as cause disease themselves.

As always I could be wrong, but I hope not since our test is tomorrow :p
I double checked the Heartworm Society website. Here's what they say:
"Continuous monthly administration of prophylactic doses of ivermectin, moxidectin and selamectin is effective in reducing the life span of juvenile and adult heartworms. ...
If arsenical therapy is declined, a lengthy course of prophylactic doses of aforementioned macrocyclic lactones will gradually reduce the number of adult heartworms. Should long-term macrocyclic lactone administration be considered for heartworm-positive dogs, exercise should be greatly restricted and the dog should be examined by a veterinarian at least once every four to six months until confirmed to be free of heartworms."

So you're right that they are still producing microfilariae, and can still transmit the infection to mosquito vectors. But it is an accepted method of treatment, and one I've personally seen work - we have a number of dogs that are now heartworm negative after being on long-term Heartgard. Then again, there are people on the internet that say using Black Walnut tincture is an effective preventative, so it always pays to check your info. :laugh:

There's new research that combining slow-kill or fast-kill methods with doxycycline may be effective because of the Wolbachia bacteria that many of the D. immitis worms harbor. Killing the Wolbachia can effectively sterilize the female worms, and that part of the side effects from dying worms in a dog is due to the release of Wolbachia endotoxins - the aim is to treat with Doxy first to reduce the Wolbachia so that as the worms die, they aren't releasing the bacteria into the dog's system. I've read studies about this being effective in a worm called Onchocerca volvus, which is also a filarial worm that infects humans. I haven't known any vets that actually USE doxy as part of the protocol, but I'm interested to see where it goes.
 

DVMDream

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I double checked the Heartworm Society website. Here's what they say:
"Continuous monthly administration of prophylactic doses of ivermectin, moxidectin and selamectin is effective in reducing the life span of juvenile and adult heartworms. ...
If arsenical therapy is declined, a lengthy course of prophylactic doses of aforementioned macrocyclic lactones will gradually reduce the number of adult heartworms. Should long-term macrocyclic lactone administration be considered for heartworm-positive dogs, exercise should be greatly restricted and the dog should be examined by a veterinarian at least once every four to six months until confirmed to be free of heartworms."

So you're right that they are still producing microfilariae, and can still transmit the infection to mosquito vectors. But it is an accepted method of treatment, and one I've personally seen work - we have a number of dogs that are now heartworm negative after being on long-term Heartgard. Then again, there are people on the internet that say using Black Walnut tincture is an effective preventative, so it always pays to check your info. :laugh:

There's new research that combining slow-kill or fast-kill methods with doxycycline may be effective because of the Wolbachia bacteria that many of the D. immitis worms harbor. Killing the Wolbachia can effectively sterilize the female worms, and that part of the side effects from dying worms in a dog is due to the release of Wolbachia endotoxins - the aim is to treat with Doxy first to reduce the Wolbachia so that as the worms die, they aren't releasing the bacteria into the dog's system. I've read studies about this being effective in a worm called Onchocerca volvus, which is also a filarial worm that infects humans. I haven't known any vets that actually USE doxy as part of the protocol, but I'm interested to see where it goes.
I knew that higher doses of Heartguard could eventually kill off adult worms but in the end wouldn't the costs be near the same? And then what would you use in collies because you can not give them ivermectin. I also knew that most dogs that die in treatment tend to die from the endotoxins from the Wolbachia bacteria. I am curious as to why doxy then has not been added to HW treatments if it can effectively reduce the amount of Wolbachia released by the adult worms it seems like a good idea to add it to the treatment. Unless killing the bacteria releases the endotoxins. Does the bacteria actually infect the dog or is it just the endotoxins that the bacteria releases that has an effect on the dog?
 
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Whyevernot55

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I knew that higher doses of Heartguard could eventually kill off adult worms but in the end wouldn't the costs be near the same? And then what would you use in collies because you can not give them ivermectin. I also knew that most dogs that die in treatment tend to die from the endotoxins from the Wolbachia bacteria. I am curious as to why doxy then has not been added to HW treatments if it can effectively reduce the amount of Wolbachia released by the adult worms it seems like a good idea to add it to the treatment.
I would imagine that the cost difference largely depends on the size of the dog. The Heartgard is probably still cheaper over the course of treatment, but since the dog will be on heartworm preventative for the rest of its life, well then it's always going to cost money.
I don't know what you'd use in Collies. I suppose they'd have to have the Immiticide treatment as opposed to slow kill. They can be on Interceptor, because that's milbemycin oxime, right? I wonder if that has any effect on adult heartworms.
I also don't know why I haven't heard of doxy being used more - it seems like it makes a lot of sense no matter what method you're using (slow or fast kill). I just haven't seen it done. Maybe somewhere it's being used commonly? Is there anyone here that knows a vet that uses it in conjunction with adulticide treatments? I couldn't find anything on VSPN, but maybe there's info on VIN about it.
Based on what I can find about Wolbachia, it's the endotoxins that effect the dog, not the bacteria themselves. When the dog is treated with Doxy prior to treatment, the endotoxins are cleared by the adult worms harboring the bacteria, so when adulticide treatment begins and the worms die, there are fewer Wolbachia to effect the dog. There's also some evidence that killing off the Wolbachia will kill the worms harboring them because they have a mutualistic relationship. I know it's been studied in human filarial worms, but I don't know the extent of studies in canine heartworms.
Anyone else who has experience with this? I'm going by what my clinic does and my boss's preferences for treatment, and what little research I can find. And sifting through the craziness on the internet about homeopathic methods.
 

twelvetigers

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We do a doxy+pred regimen for a month before the treatment.

I think it's just the endotoxins - Wolbachia are just parasite parasites. :hungover:

The Dr was telling me why she had decided to start doing doxy, and she said something about some parasite that the worms have... then she paused and said she couldn't think that it was called, but it started with a W. I was like, "oh yeah, wolbachia?" Lol. It's fun when you get to do that!
 

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We do a doxy+pred regimen for a month before the treatment.

I think it's just the endotoxins - Wolbachia are just parasite parasites. :hungover:

The Dr was telling me why she had decided to start doing doxy, and she said something about some parasite that the worms have... then she paused and said she couldn't think that it was called, but it started with a W. I was like, "oh yeah, wolbachia?" Lol. It's fun when you get to do that!
Ha! Nifty - it's neat to hear that that's actually in practice. Is your clinic doing the Immiticide treatment for positive dogs?
 

twelvetigers

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Yeah. I've heard of the slow-kill method but we generally don't prescribe to that. It's hard to determine the severity of the infection, especially in an older dog - the only indicator we have is the darkness of the dot on the HWT, and that's probably not a great indicator.
 

Whyevernot55

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Most of our HW+ patients have been young rescue dogs with no symptoms, so a small load is typically assumed, but without testing there's just no way to know.
Are you using the snap tests? How do you like them? We send out for the antigen testing because we've heard a lot of mixed reviews on the snap testing.
 

twelvetigers

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We used to use the 3-in-1 HW-Lymes-Ehrlichia snap test but now we use the VetScan HW tests (with no snapping :hungover:). We've only been using the latter for about a month. We switched because even when we tell the owners that their dog is being tested for all these things, it's still just a HWT for most people and the other things just go in one ear and out the other. Plus, the Ehr+ dogs we've found rarely end up being treated, for whatever reason. Lymes is really rare in OK.

I think I like snap tests better - Just a personal preference, though.
 

Whyevernot55

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You mean a hyperparasite. ;)
*beats self over head with parasite textbook*

I'm in a parasitology class at the moment, which is incredibly interesting when we talk about parasites that affect animals. Talking about human parasites just makes me paranoid about traveling. Meanwhile, I'm watching, Survivorman reruns going "OMFG DON'T GET IN THAT WATER! What if you get Naegleria and DIE!" while my boyfriend cries.

twelvetigers, I've never tried any of the in-house rapid tests, but I wish we'd get to try some. We basically don't have Lyme or Erlichia up here so that'd be kind of silly.
 

david594

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I think it's just the endotoxins - Wolbachia are just parasite parasites. :hungover:
If the D. Immitis cannot reproduce without the wolbachia "parasite", are they actually a parasite? ;)

You guys should do a search on the new heartworm treatment protocol recommended at the 2009 NAVC. It was a 6 month course using doxy, heartgard, and immiticide.
 

JuniorJumper

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We use doxy at the clinic I work at. We had a HW+ dog get tested after a 3 week course of doxy and 4DX turned up negative. We didn't end up needing to do Immiticide injections and instead continued it on monthly Heartgard Plus.

Another benefit of the doxy is that it is cheap (free at pharmacies in my area) and obviously less painful than the Immiticide injections. The vets where I work are huge fans of it :)
 

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*beats self over head with parasite textbook*

I'm in a parasitology class at the moment, which is incredibly interesting when we talk about parasites that affect animals. Talking about human parasites just makes me paranoid about traveling. Meanwhile, I'm watching, Survivorman reruns going "OMFG DON'T GET IN THAT WATER! What if you get Naegleria and DIE!" while my boyfriend cries.

twelvetigers, I've never tried any of the in-house rapid tests, but I wish we'd get to try some. We basically don't have Lyme or Erlichia up here so that'd be kind of silly.
Have you watched the show Monsters Inside Me. I am normally really good at guessing what parasite is affecting the people in the show.

I had a love/hate relationship with my parasitology class. Our prof was evil he made us remember the class, sub-class, order, sub-order, genus and species of all parasites and some parasites we had to know phyla and family. As well as having to know the life cycles. So it was look into microscope. See some parasite. Questions would be what sub-class does this parasite belong to? Then the second question would be what life cycle is this parasite in when it is in _____? Then repeat 49 times around in a circle (always one taxa question and one life cycle question). This was just for the lab part of it. I thought it was an interesting class, but my brain was about to explode by the end of it.
 

Whyevernot55

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Have you watched the show Monsters Inside Me. I am normally really good at guessing what parasite is affecting the people in the show.

I had a love/hate relationship with my parasitology class. Our prof was evil he made us remember the class, sub-class, order, sub-order, genus and species of all parasites and some parasites we had to know phyla and family. As well as having to know the life cycles. So it was look into microscope. See some parasite. Questions would be what sub-class does this parasite belong to? Then the second question would be what life cycle is this parasite in when it is in _____? Then repeat 49 times around in a circle (always one taxa question and one life cycle question). This was just for the lab part of it. I thought it was an interesting class, but my brain was about to explode by the end of it.
I've never seen it...now I'll have to download a season!

I hate my professor because she just can't TEACH, and has absolutely no consideration for her students. Our lab TA hasn't got a clue what he's doing and he gets frustrated easily. Our first lab practical of the semester was a disaster. "Name the genus and species of this blob under the microscope that looks nothing like what you saw in class or in your atlases!" Thank goodness we don't have to know that much taxonomy!
 

DVMDream

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I've never seen it...now I'll have to download a season!

I hate my professor because she just can't TEACH, and has absolutely no consideration for her students. Our lab TA hasn't got a clue what he's doing and he gets frustrated easily. Our first lab practical of the semester was a disaster. "Name the genus and species of this blob under the microscope that looks nothing like what you saw in class or in your atlases!" Thank goodness we don't have to know that much taxonomy!
Our prof had told us we would only need to know phylum, genus and species. Then on the first practical there were a bunch of class, order, sub-class and sub-order questions. The entire class was pissed. The prof just said that he had changed his mind and that we needed to know everything. :mad: The final cumulative practical was a pain in the ass. All we knew was that every parasite we had learned could be on the final and he could ask anything about that parasite that he wanted. I had a good stack of around 300 notecards for that class...kind of wish I still had those.
 

Vet Engineer

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As far as any of the slow kill methods go, I was under the impression that, essentially, they keep the heartworms from proliferating, i.e. only the adult heartworms that are in the dog live and everything else dies. Eventually the adult heartworms die (of old age? hahaha not sure on that) and then your previously hw+ dog is now hw-.

I thought oral ivermectin couldn't ever kill adult heartworms, regardless of the dose. Is that accurate? I feel like I have some reading up to do before I head down to A&M in August!
 
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Looks like the OP is in Texas, which has TONS of heartworm. I'm in Cleveland - we NEVER used to see heartworm, but it's become a lot more prevalent in the last 5 years. After Hurricane Katrina, a lot of those animals came up here - and all over the country, really. And 99% of those dogs were heartworm positive, so everywhere they went, the local mosquito population picked it up and now it's more prevalent in areas that it never used to exist. We saw at least 5 cases in 2009, whereas in the past we saw maybe 1 or 2 a year.

5 cases in a year? Wow. I live in the deep south and it is not uncommon to see 4 or 5 heartworm cases a day! The clinic I work at is in a pretty well off area, but we also work with 4 breed specific rescue groups so most of the cases that we see are rescue. Of course, there are a few clients that forget to give a pill for a couple of months, or the clients that don't give the dog any type of prevention or test them until it is really too late and the worm burden too heavy and irreversible damage has been done.

Our clinic had Immiticide on back order for like 4 months not being able to get any at all. Now we can get limited quantities when a client's dog is diagnosed, but we are unable to get it for our rescue dogs.

While we were on back order all heartworm positive dogs were given iverheart every 2 weeks and 30 days of doxy every 3 months until they can get the adulticide treatment. We are still doing this with our rescue dogs .

We also give dogs getting the adulticide treatment doxy for 1 month before begining the adulticide treatment.
 

Vet Engineer

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I wonder if the clinic where I work is forgetting something? I've probably seen 10-15 cases of heartworm treatment and we have never given doxy! Although, besides injection site pain, I have never witnessed any side effects even without the doxy.
 
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I work at a military installation small animal clinc in Georgia. We have heartworm positive test quite often. I have seen at least 8-12 in the past 6 months. It is really unfortunate. At any rate we too have ZERO Immiticide but we have been starting dogs on the "slow method" as well. We are giving them a combo of Doxy and Heartgard. The amount of Heartgard is increased to 1 chewable every 2 weeks (or twice a month) and the amount of doxy varies on the animal. We give the 2 together for several months. With dogs that have been on ZERO Heartgard we start them off with a (free trial) puppy size 1 time, then move them up slowly to the appropriate size one step at a time. So the first time is a puppy size, then 2 weeks later the 26-50 and so on.. if needed to reach the appropriate size for their weight. (I call it a puppy size since it is a free puppy kit we get from the company)

As far as results we have been testing animals 4+ months later and we have seen some that have come back negative after the treatment. As far as cost goes it is fairly cheap because we only serve military and our prices for products are typically cheaper particularly for these products.

On a last note, I have also heard that they are administering Immiticide for those "critical" cases that are in need. There is a form of sorts to fill out from the vet who sends it in and can apparently obtain the Immiticide. I haven't seen any come through our doors that are showing any signs of an immediate need for the Immiticide and we haven't orderd any that I am aware of. We will have to weather the storm with everyone else I guess

Oh I forgot! I have heard that the combonation of the 2 meds does something to the digestive tract of the heartworm therefore not allowing it eat or digest properly which then leads it to slowly die... again this is only what I have heard in conversations with other vets.
 

rugbychick16

KSU CVM Class of 2012
10+ Year Member
5+ Year Member
Feb 15, 2009
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Awesome website for anyone interested in heartworms
http://www.heartwormsociety.org/#


Some info on the slow kill method, from the website and my parasit notes-Interesting to read your reports here on what you've seen since I had gotten the idea the slow kill method wasn't effective at all. But with the shortage, there aren't alot of other good options.

Prolonged (16 – 30 months) monthly administration of the macrocyclic lactone (macrolides) preventives Ivermectin (6µg/kg) or Ivermectin & pyrantel pamoate killed 56 – 98% of experimentally transplanted 7 -month-old adult D. immitis and 71% of D. immitis in naturally infected dogs. The adulticide effect of Ivermectin generally requires more than 18 months of continuous administration before 40 - 50% of worms are eliminated . During this time infection persists and continues to cause disease. American Heartworm Society – “long term continuous administration of Ivermectin generally is not a substitute for conventional arsenical adulticide treatment. ” The results of a recent study indicates that such long -term therapy should not be used in dogs with signs of heartworm disease or very active dogs, and if used in asymptomatic dogs, the dogs should be examined by a veterinarian and radiographic evaluations conducted at least once every four to six months until all of the worms are dead. In addition exercise must be restricted in these dogs. Not an FDA approved use.